LINC00629, a KLF10-responsive lncRNA, promotes the anticancer effects of apigenin by decreasing Mcl1 stability in oral squamous cell carcinoma

Chun Shi; Changhong Ma; Chunmei Ren; Na Li; Xiaotong Liu; Yahan Zhang; Yulong Wang; Xiaodong Li; Peng Lv; Chuanchun Han; Xiaojie Li

doi:10.18632/aging.204396

LINC00629, a KLF10-responsive lncRNA, promotes the anticancer effects of apigenin by decreasing Mcl1 stability in oral squamous cell carcinoma

Aging (Albany NY). 2022 Nov 28;14(22):9149-9166. doi: 10.18632/aging.204396. Epub 2022 Nov 28.

Authors

Chun Shi¹, Changhong Ma², Chunmei Ren¹, Na Li³, Xiaotong Liu¹, Yahan Zhang⁴, Yulong Wang⁴, Xiaodong Li⁴, Peng Lv¹, Chuanchun Han⁴, Xiaojie Li¹

Affiliations

¹ College of Stomatology and The Second Hospital, Dalian Medical University, Dalian 116027, China.
² Department of Otorhinolaryngology, The First Affiliated Hospital, Dalian Medical University, Dalian 116027, China.
³ National-Local Joint Engineering Research Center for Drug-Research and Development (R&D) of Neurodegenerative Diseases, Dalian Medical University, Dalian 116044, China.
⁴ Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116027, China.

Abstract

Apigenin, a naturally occurring flavonoid, is known to exhibit antitumor activity in many cancers. However, the regulatory mechanism of apigenin and the long noncoding RNAs (lncRNAs) altered upon apigenin treatment in oral squamous cell carcinoma (OSCC) remain unclear. In this study, we found that LINC00629 was significantly upregulated in response to apigenin treatment. Upregulated LINC00629 enhanced the growth-suppressive and proapoptotic effects of apigenin on OSCC cells by interacting with Mcl1 and facilitating its degradation. Subsequently, our data indicated that KLF10, an important transcription factor, directly bound to the promoter of LINC00629, facilitating its transcription and contributing to apigenin-induced LINC00629 expression. Collectively, these results suggest that the KLF10-LINC00629-Mcl1 axis plays an important role in the anticancer effects of apigenin.

Keywords: LINC00629; LncRNA; Mcl1; OSCC; apigenin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apigenin / pharmacology
Apigenin / therapeutic use
Carcinoma, Squamous Cell* / drug therapy
Carcinoma, Squamous Cell* / genetics
Carcinoma, Squamous Cell* / metabolism
Cell Line, Tumor
Cell Proliferation / genetics
Early Growth Response Transcription Factors / genetics
Early Growth Response Transcription Factors / metabolism
Early Growth Response Transcription Factors / pharmacology
Gene Expression Regulation, Neoplastic
Head and Neck Neoplasms* / genetics
Humans
Kruppel-Like Transcription Factors / genetics
Kruppel-Like Transcription Factors / metabolism
MicroRNAs* / metabolism
Mouth Neoplasms* / drug therapy
Mouth Neoplasms* / genetics
Mouth Neoplasms* / metabolism
Myeloid Cell Leukemia Sequence 1 Protein / genetics
Myeloid Cell Leukemia Sequence 1 Protein / metabolism
RNA, Long Noncoding* / metabolism
Squamous Cell Carcinoma of Head and Neck / genetics

Substances

RNA, Long Noncoding
Apigenin
MicroRNAs
MCL1 protein, human
Myeloid Cell Leukemia Sequence 1 Protein
KLF10 protein, human
Kruppel-Like Transcription Factors
Early Growth Response Transcription Factors